Does NMN actually reverse “age” and if so, what does that mean?

If age is another measure of time passed then it would be naïve to consider any supplement, intervention or drug making a dent on the process, hence we must look at age as physiological processes failing or worsening as time passes.

By looking at age as a predictor of increased/increasing disease risk through DNA methylation change Muhdo have managed to get the “nitty gritty” information on what effect, if any, NMN has on gene expression and if it lives up to its name as the king of anti-ageing.

Muhdo analysed 189 individuals (76F/113M) within +/- 5 of a mean chronological age of 51 who have been taking solely NMN at variable dosages for a minimum of 10 months with no known diagnosed disease and no dietary restrictions against a cohort of 1,156 (386F/770M) within +/- 5 of a mean chronological age of 51 who have taken no supplements for the past 12 months, have no known diagnosed disease and have no dietary restrictions.

Results:

When measuring the certain genes across their respective CpG sites used in the majority of epigenetic age clocks that are robust markers of ageing (i.e. change with time):

C1orf132 – No effect

ELOVL2 (this consists of a mean of two sites) – Moderate positive methylation difference.

OTUD7A, CAM5, PRLHR, GRM2, TRIM59 – No effect

DNAH9 – Significant positive methylation difference.

When analysing both cohorts on an epigenetic clock (Muhdo MethylPace V1) there is a small positive difference between both groups when corrected for chronological age.

NMN cohort – absolute mean biological age = 52.4 yrs
Comparative cohort – absolute mean biological age = 56.1 yrs

Everything else

Muhdo analyses 850,000~ CpG sites in the majority of analysis and therefore picked up the changes across all these sites, below are some of the genes with the highest significant change in the NMN cohort, what these do and if the significance is positive or negative.

GHSR – significant/positive – effects healthy growth hormone production, appears to be related to a reduction in metabolic diseases, healthier BMI, better cardiac function and increased muscle strength

CALB1 – significant/unknown – unknown impact on the sites, however the encoded protein when depleted is associated with neurodegeneration

HAGLR – significant/positive – effects pain response, neurologic pain and may impact cancer

ZHX2 – significant/positive – appears to improve both brain & eye health and protect against DNA damage from environmental stressors

GRM2 – significant/positive – appears to improve brain health and mental wellbeing, may improve the effects of certain substances

NMN appears to have some impact on genes that are known to change with age (time), this impact appears to be positive as it brings the sites to methylation levels that are younger than the individual’s actual chronological age.

Therefore, stating that NMN reverses ageing is not untrue, NMN certainly has a positive effect on ageing, it is not the Holy grail by any stretch but should probably be strongly considered for the purposes of aiding in slowing epigenetic ageing progress.

In more significant, probably more important analysis NMN appears to effect genes that are associated with disease and health, this effect is much stronger when compared with the non-NMN group and stretches from general wellbeing to anti-pathology.

The effect NMN has on GHSR methylation may be the primary reason it appears to make people subjectively feel younger.